OVERALL University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health Disparities PROJECT SUMMARY/ABSTRACT The goal of UCaMP is to establish and characterize at least 200 patient-derived cancer xenografts (PDXs), and utilize these PDXs in preclinical testing of single agents and drug combinations that help guide future clinical decision-making emphasizing the largest racial/ethnic minority populations residing in California: Hispanic/Latino Americans [HLAs], Asian American/Native Hawaiian/Pacific Islander [AANHPIs], and African American [AAs] compared to Non-Hispanic Whites [NHWs]. We have established an accomplished transdisciplinary research team with an outstanding infrastructure that includes a University of California-wide central IRB system called Reliance and strong preliminary data to support the proposed PDX and cancer disparities research, thus allowing our results to be easily translated to clinical trials. UCaMP is comprised of four University of California NCI-designated Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center (UC Davis), UC Los Angeles Jonsson Comprehensive Cancer Center (UCLA), UC Irvine Health Chao Family Comprehensive Cancer Center (UC Irvine), and UC San Francisco Helen Diller Family Comprehensive Cancer Center (UCSF). Our collective strengths include complementary expertise in PDX development and drug testing, cancer health disparities, and clinical trial development robustly supported by cores for PDX, Pilot Studies, Bioinformatics, and Administration. We will achieve our goal through two Research Projects. Project 1 - Characterizing Treatment Responses with PDX Models for Gastric and Liver Tumors, specifically addresses cancer health disparities in gastric cancers (GC) and liver cancers (LC) that disproportionately affect all racial/ethnic minorities especially in HLA and AANHPI populations. By understanding the genetic and response differences among HLA, AANHPI compared to NHWs, we could enhance the precision of therapeutic treatments, identify resistance-associated biomarkers, and study resistance mechanisms to targeted therapies. Project 2 - Characterizing Treatment Responses with PDX Models for Lung and Bladder Tumors focuses on treatment disparities between AA and NHW patients to identify therapies targeting common genetic alterations (e.g. PI3K pathway) and to reveal targeted therapy resistance mechanisms for lung squamous cell carcinoma (LSCC) and advanced bladder cancer (aBC).